Hearing and the auditory pathway

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					          The Auditory System

     February 23, 2010
         Brad Alger

Most simulations can be found at
                                    What is sound?
As a vibrating body, say the red piston below, moves right and left, a series of
waves is set up in air (usually) as the air molecules are briefly forced together (as
the piston moves right) and the apart (as the piston moves left).

                     Air pressure


- Any vibration transmitted to the ear either via the air (or water!) or directly through the bones of the
head (bone conduction, “hearing yourself speak”) can generate auditory sensations.
     Dimensions of acoustic input

Sound can be characterized by a few attributes,
1- Sound location: where is it coming from?
       In the horizontal direction (azimuth), use
       - Interaural Time Difference for low frequencies
       - Interaural Level Difference for high freqs (head shadow)
2- Loudness: how much energy is deposited on the eardrum
3- Pitch: is determined by the frequency of a pure tone.
4- Timbre: the aspect of the sound which is neither loudness nor
       pitch (vague!). Its “quality”, “color” – how you can
       distinguish between the sounds of two different kinds of
       instruments (trumpet, saxophone) that are playing the same
Our hearing range goes from 20 Hz to 20 kHz. However, at the extremes, we
hear only very loud (100 dB) sounds.

-a threshold shift by 15 dB is
considered abnormal (hearing
- we loose our sensitivity as we
get older… Upper limit of
hearing goes down 1Hz/day.
Humans hear sounds from 20 Hz to 20 kHz

 Air-borne sounds are small fluctuations in air pressure. At the
threshold of hearing for a 17 yo male at 1 kHz, the fluctuations
correspond to 10-13 of an atmosphere. Sound at threshold of pain has
power 1012 higher! In other words, the dynamic range of the sense
of hearing is 1012 !

Decibel (dB) level is dB = 20 log10 (Pr/Prref). 0 dB is defined as
10-13 Atmosphere, or 20 mPa.
This reference level is called SPL, or standard pressure level.

Threshold of pain is 110 dB.
 30 dB = inside bedroom, 55 dB = conversation level, 75 dB = inside
a car on highway, 100 dB = behind a loud motorcycle
   Comparisons among the inner ear organs
            (vestibular, auditory)

System       Organ     Stimulus       Receptor     Sensory   Overlying
                                                     surface   membr
Vestibular   Utricle   Linear         Hair cells   Macula      Otolithic
                       Acceleration                               organ
Vestibular   Saccule   Linear         Hair cells   Macula      Otolithic
                       acceleration                               organ
Vestibular   Semi.     Angular        Hair cells   Ampullary   Cupula
               Circ.   (rotational)                crest
             Canals    acceleration                (crista)
Auditory     Cochlea   Sound          Hair cells   Organ of    Tectorial
                                                      Corti    membrane
                Entering the ear

The hearing organ is divided into 3 parts:
- [E] the outer ear: pinna, concha and ear canal (auditory meatus)
- [M] the middle ear, with 3 ossicles for sound transduction
- [I] the inner ear: cochlea
               The outer ear

Sound waves, filtered by the pinna, concha and auditory
meatus (ear canal) and set the tympanic membrane (ear drum)
in motion.
                  The middle ear I
                         The eardrum (4) separates the external auditory
                         canal from the middle ear. The oval window
                         (hidden by the stapes footplate: (3)) and the round
                         window (5) separate the middle and inner ears. The
                         ossicular chain: malleus (1), incus (2) and stapes
                         (3) links the eardrum to the oval window. The
                         surface ratio of eardrum to oval window (20/1)
                         allows an adequate energy transfer of the sound
                         pressure between the air and the fluids of the inner
                         ear. The eustachian tube (6) allows equilibration of
                         air pressure between the middle ear and the ambient
The ossicles match the   world.
impedance between
the ambient air and
the cochlear fluids
                       The middle ear II
                                            The surface of the tympanic
                                            membrane observed from inside the
                                            middle ear. The attached arm of the
                                            malleus is seen in the centre.

                                              As a sound comes down the ear canal the
                                              ossicle chain moves about an axis parallel
                                              to the eardrum, and moves the oval
                                              window of the cochlea. As the oval
                                              window bulges inward, the round window
                                              bulges outward to relieve the pressure.

Animation at
The middle ear III

      2 muscles: Tensor Tympani and Stapedius.
      -Tensor Tympani innervated by trigeminal
      (motor), pulls (adds tension) the ear drum.
      - Stapedius: innervated by facial nerve, tilts
      stapes. Bell‟s palsy can cause hearing deficits.
      -Contraction of middle muscles results in
      attenuation of low-frequency sounds mostly.
                        The Cochlea
                                 Not bone
Vestibule and cochlea: two                            bone
sensory organs of the inner ear

Two sensory organs are located in the
inner ear. The vestibule is the organ of
equilibrium and the cochlea the organ
of hearing. They share similar
morphological and physiological
properties such as endolymph, hair
cells and mechano-transduction.
The schematic drawing represents the
osseous (top left) and membranous
(seen by transparency in the main
drawing) labyrinths.                     5. Cochlear duct 6. Helicotrema
                                         10. Oval window 11. Round window
                                    12. Vestibular duct (scala vestibuli)
                                    13. Tympanic duct (scala tympani)
                        The Cochlea II
The bone has been removed to visualize the
vestibule (1), the VIIIth nerve (2) , and the basal
portion of the cochlear duct (3), housing the
organ of Corti. The rest of the cochlea (4) is
covered by the bony capsule. The VIIIth nerve
is formed by the vestibular and cochlear
nerves which merge before entering the brain.

                                 Cochlea from a human fetus ( 5 months)

                                 The bony capsule has been dissected out, showing
                                 the 2 1/2 coils of the membranous labyrinth (35
                                 mm in length). The oval (blue arrow) and round
                                 (yellow arrow) windows are indicated.

                                 scale bar: 0.5 mm
                     Cochlear Fluids
Perilymph and endolymph
The endolymph ( red) and perilymph (blue) differ in their ionic contents.

                                  The endolymph, with a high K+ and a low Na+
                                  concentration, resembles the cytosol.
                                  In contrast, the perilymph is like the extracellular
                                  medium, with a low K+ and Na+ content. The differing
                                  ionic composition results in an ~ 80 mV difference in
                                  potential between the endolymph and the perilymph.
         In the cochlea: organ of Corti

Cross section of a turn of the

The cochlear duct (1) is isolated from
the scala vestibuli (2) and scala
tympani (3) by Reissner's (4) and
basilar (5) membranes respectively.
The organ of Corti is covered by the
tectorial membrane (6) floating in
the endolymph. Also shown are the
stria vascularis (7) and the fibres (8)
going to the spiral ganglion through
the bony spiral lamina (9).
          The organ of Corti: hair cells
                                                     1-Inner hair cells (transduction)
                                                     2-Outer hair cells (amplification)
                                                     3-Tunnel of Corti (support)
                                                     Organ of Corti = 1&2&3&8&…
                                                     4-Basilar membrane (pliant)
                                                     6-Tectorial membrane (pliant)
                                                     7-Deiters' cells (support cells)
                                                     9-Hensen's cells (support cells)
                                                     10-Inner spiral sulcus

                                                     IHC = Inner Hair Cell
                                                     OHC = Outer Hair Cell

The tectorial membrane is a gelatinous structure, in which the tip of the OHC stereocilia are
embedded. It has a groove into which the tip of the IHC stereocilia fit.
                        Inner hair cells I

                          OHC                         IHC

View from above of a small part of the basilar membrane, with the tectorial membrane
removed. There are three rows of OHC, and one row of IHC (on the modiolus side). Humans
have about 12,000 OHC and 3,500 IHC. They share with neurons the inability to proliferate
once differentiated - the final number of hair cells is reached very early in development (around
10 weeks of fetal gestation).
                       The middle ear II
                                            The surface of the tympanic
                                            membrane observed from inside the
                                            middle ear. The attached arm of the
                                            malleus is seen in the centre.

                                              As a sound comes down the ear canal the
                                              ossicle chain moves about an axis parallel
                                              to the eardrum, and moves the oval
                                              window of the cochlea. As the oval
                                              window bulges inward, the round window
                                              bulges outward to relieve the pressure.

Animation at
                         The Cochlea III
Section through the bony cochlea and the
cochlear duct.
(1) The scala media, containing the
organ of Corti
(2) The scala vestibuli, separated from the
scala media by a very thin membrane (of
(3) The scala tympani, providing the
„pressure return‟ to the round window
(4) Neurons in the spiral ganglion travel
centrally as
(5) Fibers of the VIIIth nerve.
The red arrow is from the oval window,
the blue arrow points to the round window.

      The scala media or cochlear duct is an endolymph-filled chamber,
      separating two perilymph-filled chambers (vestibuli and tympani),
      themselves communicating at the helicotrema.
Activation of the organ of Corti

    When a sound causes the ossicles to move the oval window, the
    vibration is transmitted up the „scala vestibuli/scala media‟.
             The organ of Corti II

When a wave travels up the cochlea, the relative motion of the
basilar and the tectorial membrane causes fluid to move between
them. Movements in the cochlear fluid are amplified by the
OHC („pulling‟ on the tectorial membrane), causing an oscillation
of the tips of the stereociliae of the inner hair cells, which are
freely floating.
Movements of the oval window set up fluid motions that cause a
(traveling) wave of deflections in the basilar membrane. The
amplitude of the wave peaks at a point along the membrane that is
different for each (pure) frequency tone. HCs at that point are
maximally stimulated.
The basilar membrane maps (a tonotopic map) the sound spectrum along its
length. High frequency sounds are represented at the basal end, near the oval
window. Low frequency sounds are represented at the apical end, near the
helicotrema (a small hole that connects the scala vestibuli and the scala tympani
at the tip of the cochea).
          Organ of Corti: innervation
Both types of hair cells are innervated by specific afferent and efferent systems
forming a loop to and from the brainstem. The role of the innervation of the outer
hair cells is unknown.

  Innervation of inner (1)
  and outer hair cells (2)

Radial afferents (blue) and the lateral efferents (pink) innervate the IHC;
spiral afferents (green) and the medial efferents (red) innervate the OHC.
                   Hair Cell Innervation

Schematic representation of the hair cell
afferent innervation

Most, 95%, spiral ganglion neurons have single
endings onto IHCs. There are about 10 type I
fibers per IHC. Type I, myelinated.

Small, unmyelinated neurons connect (each on to
about ten OHCs). Type II, unmyelinated. When
electrically stimulated, thresholds are raised.
              The Auditory Pathway
Simplified version of the anatomy
of the ascending part of the primary
part of the auditory pathway.
The Auditory Pathway: Brainstem
      Auditory nerve -> Cochlear Nucleus -> Superior Olive

The first relay is in the cochlear nuclei
(CN) in the brain stem, which receive
Type I spiral ganglion axons.

There are 3 parts of the CN (PVCN,
      The Brainstem: Superior Olive
                 Cochlear Nucleus -> Superior Olive
The second major station in the brain stem
is the Superior Olivary Complex (SOC):
most auditory fibres synapse there having
already crossed the midline.

The SOC has two major nuclei, the Medial
Superior Olive, and the Lateral Superior

                                       Three primary cues are important for sound
                                       localization: interaural time disparities
                                       (ITDs), interaural level disparities (ILDs),
                                       and spectral cues (from the pinna). The two
                                       binaural cues, ITDs and ILDs, are encoded in
                                       the brainstem in two parallel circuits that
                                       start in the anteroventral cochlear nucleus
                  The Superior Olive
The medial superior olive (MSO) encodes Interaural Time Disparities (i.e.,
sound gets to one ear first) using a coincidence model (below right).
Interaural Level Disparties (sounds are louder in one ear than the other) are
encoded in the lateral superior olive (LSO) and medial nucleus of the trapezoid
body (MNTB).

     ITD         ILD
  Superior Olive -> Lateral Lemniscus -> Inferior Colliculus

Next is the Lateral Lemniscus (role
unknown, and then the Inferior
Colliculus (IC).

The IC is likely involved in pitch
extraction, and in orientation reflex.
It‟s a complicated structure, with a
very strong tonotopic axis in its central

                                                       Superior Olive
Thalamus: the Medial Geniculate Body
                       Inferior Colliculus -> Thalamus

The final station before the cortex is the
medial geniculate body, MGB, in the

The activity in the MGB is strongly
modulated by the state of alertness
(sleep, drowsiness, alertness…)

Also, an important integration occurs:
preparation of a motor response (eg vocal
The end of the line: Auditory Cortex
               Thalamus -> Auditory Cortex

 The final stop is the auditory cortex,
 where the message, already largely
 decoded during its passage through the
 previous neurons in the pathway, is
 recognised, memorised and perhaps
 integrated into a voluntary response.

 In humans, the Primary Auditory Cortex
 (3) is located in the temporal area (2)
 within the lateral sulcus (1).
Tonotopic organization of AI
      Areas 41 and 42
 Principles of auditory coding
• Pitch coding
  – Frequency following – neurons fire in 1 to 1 ratio
    with sound frequency cycle. Only works for lowish
  – Volley firing – many neurons fire at regular points
    during sound wave, but not on every cycle. Group
    behavior captures pitch.
  – Tonotopic mapping – higher order neurons receive
    input from cells in lower centers that code for
    given frequencies.
• Loudness coding
  – related to the numbers of cells firing.
             The Auditory Pathway
The roles different stations along the auditory pathway, from the cochlea to
auditory cortex, are poorly understood.
As one progresses up the pathway, neurons are more and more „sluggish‟,
from frequency following firings up to 2.5 kHz in the auditory nerve down
to “envelope modulation” following response below 25 Hz in auditory
cortex. On the other hand, there are more and more neurons at each step,
from 3,500 IHCs to well over a million in auditory cortex.
For almost every afferent projection, there is a strong efferent back-
projection. For instance, the olivo-cochlear bundle modulates the activity of
OHCs. By the time one reaches the thalamo-cortical projections, there are
10 times as many projections from auditory cortex to MGB as there are
from MGB to auditory cortex.
Anatomy, pictures of auditory pathway, numbers:
Many of the pictures in this lecture:
The simulations used in this lecture:
A good reference
More than you ever wanted to know about cochlear fluids, including
where they come from, and more anatomy of the cochlea
The end.
Hearing: what makes us from other animals is our ability to communicate ideas
and concepts by the use of language. Oral communication is the natural means
of communication… “A blind person is cut off from the world of things,
whereas one who is deaf is cut off from the world of people.”

Our understanding of hearing is less developed compared
with that of other senses, in part, because the organ of hearing
is hard to access: the cochlea is buried in the petrous
temporal bone.

The parameters or dimensions that characterize acoustic signals are less
obvious than those, say, of the visual system.
                                   Inner hair cells II
                        Excitation                                    Inhibition

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                  Cinepak decompressor                             Cinepak decompressor
              are need ed to see this p icture .               are need ed to see this p icture .

  Animation                                        Animation

Movement of the cochlear fluid away from the modiolus with respect to the fixed
„Organ of Corti/Inner Hair Cell‟ complex results in a depolarization of the IHC, and
the generation of action potentials in the auditory nerve fibers, but only when the
fluid moves in that direction (half-wave rectification). The IHC are inhibited when the
fluid moves in the opposite direction.
       Inner Hair Cells: transduction I
Arrangement of stereocilia (links)
Arrangement of stereocilia in adult mammalian cochlear hair cell:
Stereocilia (around a hundred) are generally arranged in about
three rows of graded lengths. They are attached by thin tip links
(red) involved in the mechano-transduction process, and lateral
links (blue). Stereocilia are also attached by transverse (lateral)
links, both in the same row and from row to row, presumably for
stiffness of the assembly.

The tip link (red arrow) and a lateral link (blue arrow)
between medium and tall stereocilia are clearly visible. At
both ends of the tip link, a membrane condensation is seen.
These structures are involved in the
mechano-transduction process.
scale bar: 300 nm
                     Cochlear Fluids
Perilymph and endolymph
The endolymph ( red) and perilymph (blue) differ in their ionic contents.

                                  The endolymph composition, with a high K and a low
                                  Na concentration, resembles the cytosol.
                                  In contrast, the perilymph composition is closer to the
                                  extracellular medium, with a low K but a high Na
                                  content. The differing ionic composition results in a
                                  roughly 80 mV difference in potential between the
                                  endolymph and the perilymph.
     Inner Hair Cells: transduction II
From mechano-transduction to neurotransmission
Schematically, the bending of stereocilia allows K+ to flow
into the IHC, which is thus depolarised. This opens voltage-
gated Ca++ channels. Calcium is involved in
neurotransmitter (glutamate) release and also in a K+ active
exit mechanism.

Transmission electron micrograph of an IHC from a
guinea pig cochlea
Note the medially located nucleus and the randomly
dispersed mitochondria within the IHC. Afferent nerve
profiles (arrows) are seen at the base. On average, an IHC is
connected by ten boutons from afferent fibers. This number
increases in the region of best frequencies. In the bat
cochlea (the portion of the cochlea coding for echo
frequency) up to 50 boutons per IHC can be observed.
scale bar: 5 µm
            Interlude: About Hearing
-28 million Americans deaf or hard of hearing.
- Most acquired sensorineural hearing loss results from genetic predisposition. 50%
of deafness at birth is due to genetic condition. Remedy: In the US, 34,000 people
have cochlear implants; about half are children.
- Most common cause of hearing loss in children is otitis media. Three out of four
children experience otitis media by the time they are 3 years old.
- The largest group of Americans suffering from hearing loss is the elderly.
1. Age-related hearing loss = 30 to 35 % between ages of 65 and 75yr
2. 40 % of the population over the age of 75 yrs
3. 615,000 individuals with diagnosed Ménière's disease in the United States and
45,500 newly diagnosed cases each year.
- Substantial number of hearing impairments are caused by environmental factors
such as noise (Of the 28 million Americans who have some degree of hearing loss,
about one-third have been affected, at least in part, by noise), drugs (Antibiotics
from the aminoglycoside family cause severe damage to hair cells in a dose-
dependent manner), and toxins.
- Unilateral vestibular schwannomas affect only one ear. They account for 8 % of all
tumors inside the skull;
               Intermission: Pathology
-There is a critical period for development: kids with „middle ear ventilation tubes‟
can have threholds in that ear raised by 15 dB. If left in place long enough, the
result is poor binaural hearing (e.g. poor intelligibility of speech in noise)
- OHC are amplifiers. They sometimes „ring‟ on their own (the spontaneous
otoacoustic emissions you sometimes hear in your own ears). A healthy ear
generates spontaneous otoacoustic emissions.
- Tinnitus is a common problem. It can be objective (some OHC won‟t stop
oscillating), or subjective (VIIIth nerve tumor in the modiolus, Inferior Colliculus
lesion, many causes). Permanent objective tinnitus is often induced by exposure to
loud sounds.
- Increase in pressure in the cochlea (Meniere‟s disease or presbycusis) results in
stiffness of basilar membrane (?), causing elevated threshold.
            Aminoglycoside ototoxicity
1   scale bar: 12 µm   Antibiotics from the aminoglycoside family cause severe
                       damage to hair cells in a dose-dependent manner. First
                       OHCs in the first row of the basal turn of the cochlea are
                       affected (high frequencies), then progressively the other
                       rows of OHCs and then the IHCs.
                       1) SEM picture of the rat organ of Corti. Normal
                           organisation, with 1 row of IHCs (top) and 3 rows of
2                          OHCs (bottom).
                       Progressive damage of hair cells
                       2) The loss of hair cells begins with OHCs from the first
                       row in the basal turn. In humans, this would lead to mild
                       hearing loss with speech discrimination problems.
                       3) At higher dosage, the aminoglycoside kills almost all
3                      OHCs. In humans, this would lead to a 60 dB threshold
                       shift and no fine tuning. A hearing aid would easily
                       restore the gain (loudness), but not the frequency
                       selectivity (discrimination).

    scale bar: 16 µm
                              Noise trauma
Exposure to loud noise (above 90 dB) causes noise-induced hearing loss, depending on both level
of noise and duration of exposure. Hearing loss may be temporary if a repair mechanism is able
to restore the organ of Corti, or permanent when hair cells or neurons die (neuronal apoptosis or
programmed cell death) .

                       Acoustic trauma and hair cells
1                      Damage to hair cells may vary depending on level of exposure.
                       1) mild damage, restricted to stereocilia : ranging from disarray, broken
                       tip links and broken roots to fused and giant stereocilia;
                       electromechanical transduction is altered, slow repair may occur.
                       2) Severe and definitive damage, when the hair cell itself is altered and
                       disappears. The flat preparation shows a traumatised cochlea where 7 to
                       8 OHC have disappeared, together with a pillar cell (damaged area
                       outlined in blue). .
2                      High intensity impulse noise
                       Machine guns, machines and fireworks may produce impulse noise
                       above 130 or 140 dB. At these levels, an actual hole can be observed in
                       the reticular lamina, allowing merging of endolymph and perilymph and
                       leading to total deafness.

  scale bar: 20 µm

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